discovery of risk factors for type 2 diabetes in youth

Conditions: Diabetes Mellitus Type 2, Childhood-Onset

Summary: the goal of the discovery study is to provide innovative critical information regarding the unique natural history of glycemic control, insulin sensitivity, and β-cell function, and their mechanistic determinates, in obese adolescents at risk for developing type 2 diabetes.

the discovery study will extensively phenotype a large cohort of youth at-risk for type 2 diabetes, as they transition through puberty, and characterize the course of dysfunction in pathophysiological indicators that lead to type 2 diabetes. the knowledge gained from this study of the pathophysiology and epidemiology of youth-onset type 2 diabetes with deep biochemical, clinical, and psychosocial phenotyping will critically inform the design and testing of future treatment and prevention approaches.

Eligibility criteria:
inclusion criteria: screening will occur to enrich the yield of individuals who are highly predisposed to develop youth-onset type 2 diabetes and include those with all of the criteria in category a: * overweight or obesity with bmi ≥85th percentile * age 9-13 year for girls, 10-14 year for boys (inclusion younger for girls as puberty tends to start a year earlier in girls) * tanner stage 2, 3, or 4 * elevated hba1c 5.5-6.4% participants who meet all of these categories will further need to meet at least one criterion in category b: * family history of type 2 diabetes in 1st or 2nd degree relative * personal exposure to maternal diabetes (i.e., gestational diabetes mellitus (gdm) or mother with type 1 or type 2 diabetes while pregnant with participant) * hba1c ≥6.0% * severe obesity (bmi ≥99th percentile) * personal history of intrauterine growth restriction (iugr), small for gestational age (sga), or low birth weight exclusion criteria: an individual who meets any of the following criteria will be excluded from participation: * diabetes based on history, or hba1c ≥6.5% in the medical record or at screening * unable/unwilling to provide consent/participate fully * conditions predisposing to diabetes or altering the trajectory of puberty (transplant, cancer, down syndrome, turner syndrome, klinefelter syndrome, ovarian/testicular failure, etc.) * medications affecting glucose dynamics during the screening and enrollment period (oral steroids, inhaled steroids \>1,000mcg/day past month, atypical antipsychotics, topiramate) * prior treatment with insulin * use of glucagon-like peptide-1 (glp-1) receptor agonist or any weight loss medications in the 6 weeks prior to enrollment * planning treatment with glucagon-like peptide-1 (glp-1) receptor agonist or any weight loss medications * use of metformin or any glucose lowering medication for a reason other than treatment of diabetes (e.g., for pcos) in the 6 weeks prior to enrollment * known syndromic/monogenic obesity * blood disorders impacting hba1c (e.g., anemia, hemoglobin variants) * major systemic organ disease * history of bariatric surgery or currently planning bariatric surgery * current pregnancy or currently planning pregnancy * use of gnrh agonist, estrogen, or testosterone * individuals who do not speak english or spanish, given validation of the questionnaires to be utilized